Metastasis of Lung Cancer to the Oral and Maxillofacial Region: A Case Report and Review of the Literature

Introduction

Metastatic tumors to the oral region are uncommon (representing 1-2% of oral malignancies) and may occur in the oral soft tissues or in the jawbones.¹  Only 5% of all malignancies involve the oral cavity, and one percent of these malignancies are secondary to neoplasms found below the level of the clavicles.² These oral metastases are often a late-stage manifestation found in the presence of widespread disease and are associated with poor long-term prognosis, yet they are sometimes the first sign of an undiagnosed malignancy.  The rarity and severity of these metastases make the diagnosis and treatment of these tumors challenging for both the clinician and pathologist.¹ Herein, we present a case of a 75-year-old woman with poorly differentiated lung carcinoma involving the mandible, which was initially thought to be a lesion of endodontic origin, and a review of literature spanning 2014-2022.

Case Report

A 75-year-old female in apparent good health was referred to an oral surgeon by her treating endodontist for evaluation of persistent swelling of the lower left mandible. Mandibular left first molar, believed to be the source of swelling, received root canal treatment twice over the 6 months preceding the oral surgery visit (Figure 1). An accompanying computer tomography (CT) scan demonstrated reactive periostitis in the area.

Clinical examination revealed slight fullness of lower left face, with no appreciable lymphadenopathy, redness, or tenderness. Intraorally, marked expansion of posterior left mandible was noted, although the mucosal surface was intact and did not show ulceration or discoloration. 

Figure 1: Preoperative panoramic radiograph with no readily apparent lesion apical to mandibular left first molar.

Based on the clinical presentation, periapical pathology, such as periapical granuloma or radicular cyst, was suspected.  Radiographically, periapical granuloma presents with an opacity at the apex of a nonvital tooth, although early lesions may present with no radiographic evidence.³ Similar to a periapical granuloma, a radicular cyst is associated with an asymptomatic nonvital tooth, with radiographic appearance identical to that of a periapical granuloma.  Radicular cysts are more likely to be present in the anterior maxilla rather than the molar region of the mandible seen in this case.⁴ A residual radicular cyst was not considered, as this patient’s lesion was not at an extraction site or an area where an odontogenic cyst was removed. Residual cysts typically present in areas that are not properly curetted.⁵ Although it is not common for the lining of a residual cyst to undergo malignant transformation to squamous cell carcinoma, it should always be included on a differential with a residual radicular cyst when there is history of extraction or surgical removal of a cyst.⁶

A biopsy was obtained apical to the distal root of mandibular left first molar was planned to determine the cause of persistent swelling. A mucoperiosteal flap was created and reflected on posterior left buccal alveolar ridge, and a bony window was created with a low-speed handpiece and abundant sterile saline irrigation. Lesional tissue was obtained through the osseous window and submitted for histologic examination along with the bony window. Histologic examination revealed a proliferation of cells with nuclear hyperchromasia, enlargement, and pleomorphism against a background of extravasated red blood cells (Figure 2). Immunohistochemical staining demonstrated the positivity of the lesional cells for panCK, CK7, TTF-1, and Napsin A. CK20, S100, CD45, HMB45, CDX2, and GATA3 were negative. This immunohistochemical profile suggested the lung as the primary origin of the present lesion.

Figure 2: Proliferation of cells demonstrating nuclear hyperchromasia, enlargement, and pleomorphism (arrows) against a background of extravasated red blood cells (asterisks), 100x (hematoxylin-eosin).

Materials and Methods

A literature search for metastatic lung cancer cases in the oral and maxillofacial region was performed using references from January 2015 through March 2022 in PubMed, Scopus, Web of Science, and the Columbia University Libraries with combinations of the keywords metastatic lung cancer, metastatic lung carcinoma, metastasizing lung cancer, metastasizing lung carcinoma, jaw metastasis, metastasis to oral cavity, metastasis to jawbones, metastasis to oral and maxillofacial region, and metastasis to salivary glands. The selected publications were analyzed using the following factors: type of lung cancer, site of metastasis, treatment received, and outcome/prognosis. The cases were reported as case reports or reviews of the literature.

We present a review of literature on lung cancer metastases to the oral cavity. To the best of our knowledge, this is the first such literature review since the most recent publication in 2014.⁷ Results of the literature review of lung tumors metastatic to the oral and maxillofacial region are presented in Table 1.^7-51  

Results

Forty-five articles were used to identify forty-six cases.  All of the publications entered into the final review were case reports (N=46). 

Patient age was reported in forty-five of the cases.  Most metastatic tumors to the oral and maxillofacial regions were found in patients in their seventh decade (mean age for male was 62.3 years and 67 years for females). This is slightly older than the data from Hirshberg et. al, which reported the most common decades being the fifth and sixth.¹

The sex of the patients was mentioned in all of the publications.  Metastatic lung cancer to the oral and maxillofacial region was more prevalent in males (n=33) than in females (n=13; ratio, 2.54:1). This is similar to the 2.5:1 ratio cited for soft tissue metastases.¹

In line with past research, the jawbones and hard palate were more affected than the oral soft tissues (25:21), and of the bony structures in the oral and maxillofacial region, the mandible was the most frequently affected structure.  The mandible was the site of oral metastasis nineteen times (n=19) of the forty-six cases.  The posterior mandible or ramus of the mandible was particularly common.

When looking at the oral soft tissues, the attached gingiva of the maxilla was the most commonly affected site (6 cases, 28.5%), followed by the parotid gland (5 cases, 23.8%), and the tongue (4 cases, 19.0%).  The remaining soft tissue sites occurred much less frequently. 

Patients often presented with several symptoms common to past research, the most common being pain, swelling, and paresthesia.  In the event that soft tissue was involved, it was also common that bleeding or ulceration was present. 

In twenty-five of the forty-six cases, the patient was unaware of any primary cancer at the time of presentation with oral symptoms.  This demonstrates that patients can unknowingly have widespread metastatic cancer and present with symptoms that a dental provider should notice. An occult primary should be considered when a patient presents with symptoms suggestive of metastatic disease or if a lesion persists after dental treatment.  No conclusions  can be drawn regarding the frequency of distant oral metastases presenting the first symptom of metastatic disease due to bias of reporting unusual cases. 

Histological typing was done in forty-four cases.  The most common histological type was by far adenocarcinoma (n=24), followed by small cell or neuroendocrine carcinoma (n=9), mesothelioma (n=5), squamous cell carcinoma (n=5), and non-small cell carcinoma (n=1). 

In twenty-six cases there was some form of tobacco use reported in the patient history (56.5% of cases).  Twenty-four of these cases reported that the patient was either a current or former smoker and in two of the cases the patient used a form of smokeless tobacco.  It should be noted that tobacco could have been used in a greater number of the cases, but tobacco use was not specified in sixteen of the cases. 

In the reported cases chemotherapy was by far the most common treatment modality.  Chemotherapy was used in thirty-one (67.4%) of the cases.  This is to be expected as it is known that oral metastases are often a late-stage manifestation found in the presence of widespread disease.¹ Radiation therapy was used in twenty-one cases (45.7%), and surgical excision was used in twelve of the cases (26.0%).  Treatment was not specified in six of the cases, the patient declined any treatment in two of the cases, and one patient was lost to follow up. 

Metastasis of a distant primary malignancy to the oral cavity is associated with poor long-term prognosis.¹ Of the reported cases, twenty-two of the patients (47.9%)  had died prior to publication of an associated case report.  The overwhelming majority of the patients who died did so within weeks to months of diagnosis of their oral lesion.  At the time of publication ten cases (21.7%) reported that the patient was still living.  No follow-up information was provided on the patient in fourteen of the cases. 

Table 1: 2015 to 2022.Results of the literature search of lung tumors metastatic to the oral and maxillofacial region from

Discussion

Metastasis to the oral cavity may occur at any age, but is most common during the fifth and sixth decades of life. There is an almost equal sex distribution in jawbone metastases, whereas in the oral soft tissues there is a 2:1 male to female ratio. 70% of oral metastases manifest after the primary tumor becomes evident, while the remaining 30% are the first clinical manifestation of tumor spread.¹ The most common location for these metastases to the oral cavity is the mandible. This predilection is likely due to sites of bone metastasis concentrating in red marrow, as opposed to the primarily fatty marrow composition of the maxilla.⁵²

Lung cancer is one of the most malignant solid tumors. Almost 1,608,823 cases of lung cancer and 1,378,415 cancer deaths occur worldwide each year.⁵³ Lung cancer is also the most common neoplasm to metastasize to the oral cavity,² usually via blood vessels.¹ The average survival rate for metastatic lung cancer is 4 months to 1 year, with a maximum survival rate of five years.⁵⁴

Lung cancer may also metastasize to the soft tissues. These metastases can appear as dental or periodontal infections and resemble reactive lesions like pyogenic granuloma, epulis, and peripheral giant cell granuloma, or odontogenic infection.⁵⁵ For gingival metastases, fast growth, a tendency for bleeding, mechanical disorders due to tumor development, ulceration, and a patient’s clinical condition can all suggest a lesion of malignant nature.⁵⁶ Common symptoms of oral metastases to the oral cavity include a rapidly progressing lesion with potential pain and paresthesia, a bony swelling with tenderness over the affected area, dysphagia, disfigurement, and bleeding.^57,58

Gnathic metastases can be initially misdiagnosed as endodontic lesions, as was the case with our patient. According to recent literature, about 0.65%–4.22% of clinically diagnosed endodontic periapical pathoses receive a nonendodontic histopathologic diagnosis, emphasizing the difficulty and importance of identifying and classifying these lesions, particularly the malignant nonendodontic lesions (MNPLs).⁵⁹ MNPLs are common in the posterior mandible and are usually radiolucent and unilocular, with tooth mobility or bone resorption. On physical examination, metastatic jaw lesions can develop a bony swelling with tenderness over the affected area, pain, and paresthesia. Jaw metastases do not possess a pathognomonic radiographic appearance, most often presenting as lytic radiolucencies with ill-defined margins.²  Our case featured swelling of the posterior mandible as the major symptom, with no apparent radiolucency.

Conclusion

            The ages, sex, most common locations and symptoms of lung cancer metastases to the mandible in this literature review were all similar to previous research done by Hirshberg et al.¹ and others. 54% of the cases in the literature review were unaware of the primary cancer prior to the discovery of the oral lesion, compared to only 30% reported in past research. Malignant nonendodontic lesions can present similarly to many benign lesions in the oral cavity, and early detection and biopsy of these lesions are critical to improving the prognosis of these cases.

Conflict of Interest:

The authors declare no conflict of interest.

Source of Funding:

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.